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Cocaine self‐administration disrupts mesolimbic dopamine circuit function and attenuates dopaminergic responsiveness to cocaine
Author(s) -
Siciliano Cody A.,
Ferris Mark J.,
Jones Sara R.
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12970
Subject(s) - ventral tegmental area , dopamine , nucleus accumbens , dopaminergic , self administration , brain stimulation reward , mesolimbic pathway , dopamine uptake inhibitors , neuroscience , addiction , midbrain , psychology , pharmacology , medicine , central nervous system
Dopaminergic projections from the ventral midbrain to the nucleus accumbens ( NA c) have long been implicated in encoding associations between reward availability and environmental stimuli. As such, this circuit is instrumental in guiding behaviors towards obtaining maximal rewards based on previous experience. Cocaine acts on the dopamine system to exert its reinforcing effects and it is thought that cocaine‐induced dysregulation of dopamine neurotransmission contributes to the difficulty that cocaine addicts exhibit in selecting environmentally appropriate behaviors. Here we used cocaine self‐administration combined with in vivo fast scan cyclic voltammetry in anesthetised rats to examine the function of the ventral tegmental area to NA c projection neurons. Over 5 days of cocaine self‐administration (fixed‐ratio 1; 1.5 mg/kg/injection; 40 injections/day), animals increased their rate of intake. Following cocaine self‐administration, there was a marked reduction in ventral tegmental area‐stimulated NA c dopamine release. Additionally, there was a decreased augmentation of stimulated dopamine overflow in response to a cocaine challenge. These findings demonstrate that cocaine induces a hypodopaminergic state, which may contribute to the inflexible drug‐taking and drug‐seeking behaviors observed in cocaine abusers. Additionally, tolerance to the ability of cocaine to elevate dopamine may lead to increased cocaine intake in order to overcome decreased effects, another hallmark of cocaine abuse.